Objective To explore the preventive and protective effect of CGRP on focal cerebral infarction in rats.Methods Focal cerebral infarction model was made by photochemical reaction. The level of cerebral edema was assayed by measuring brain water content.Nervous system evaluation was scored by the method of Ohno, Bederson, LeWay standard. The volume of cerebral infarction and its location were determined by TTC staining.Results CGRP has significant preventive and protective effect to focal cerebral infarction which showed the nervous system scores took a favourable turn, brain edema descended and infarction volume reduced. This effect was related with the dose and the way of administration of CGRP. A single dose (1.33 BU/gBW) of CGRP didn't have significantly effective.It should be given for at least over 2 days. This protective effect did not increase when the dose increased to a certain level. As for the effect of the way of administration of CGRP, multiadministration of fewer doses CGRP was better while the total dose kept constantly.Conclusion CGRP has definite preventive and protective effect to focal cerebral infarction in rats.It has also better effective in inhibition of brain edema. However its dose should be confined in a proper level.

To observe whether plasma levels of lysophosphatidic acid (LPA) can be decreased in patients with cerebrovascular diseases after the treatment with aspirin. Methods:A total of 1,400 patients were recruited. Among them,803 patients were diagnosed as probable ischemic stroke,and 343 patients were diagnosed as ischemic stroke. Thirty-four health volunteers were used as control subjects. The levels of LPA were measured by chromatography with the combination of inorganic phosphorus quantitative method. Results: The levels of LPA in the ischemic cerebrovascular group (3.11 ± 1.55 μmol/L) were significantly higher than those in the control group (1.77 ± 1.04 μmol/L) (P < 0.001). Taking aspirin (80 mg,qd) for one month significantly decreased the levels of LPA. After stopping aspirin for one month,the level of LPA re-elevated (3.90 ± 1.09 μmol/L),was higher than that during administration of aspirin (1.93 ±0.85 μmol/L(P <0.001). Conclusions: There are close correlations between the increased levels of LPA and the platelet activation. Aspirin decreases the level of plasma LPA;this may be one of the mechanisms of aspirin in prevention against ischemic stroke.

BACKGROUND:Lysophosphatidic acid (LPA) had 3 kinds of receptors in vitro. Some researches had showed that LPA1, LPA2 and LPA3 receptors distributed widely in mouse cerebral cortex, nephritic external medulla layer and internal medulla layer, spermary, thymus, heart, lung, stomach, spleen, whereas less in liver, small intestine and skeletal muscles. Whether there are various LPA receptors in mouse VSMC membrane deserves further study.OBJECTIVE: To observe the mRNA expression of LPA receptors in vascular smooth muscle cells (VSMC).DESIGN: Observational comparative experiment.SETTING: Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: A total of 24 C57BL/6 mice aged 7-8 weeks, of either sex, with the body mass of approximately (25±3) g,were purchased from the Animal Department of Tongji Medical College, Huazhong University of Science and Technology. Trizol was purchased from America Invitrogen; dNTP Mix, Rnasin were obtained from TaKaRa; M-MLV reverse transcriptase and buffer system were from Promega; Taq DNA-polymerase and buffer system were from Biostar.Oligo(dT)18 primer were from Sangon, Shanghai. Primer sequences were designed referring to literature and nucleotide sequence database and synthesized by Sangon, Shanghai.METHODS: The experiment was conducted at the Comprehensive Laboratory, Tongji Medical College, Huazhong University of Science and Technology between August 2005 and January 2006. Mice were anaesthetized by abdominal cavity with 20 g/L ketamine (5 mL/kg). Thoracic aorta was obtained sterilely, and VSMC was cultured with adherence method. The 4th-6th passage cells were used in the trial. Cell purity was over 95%. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to determine the mRNA expression of LPA receptors gene in mouse VSMC.MAIN OUTCOME MEASURES: Detection of mRNA expression of LPA receptors in mouse VSMC and comparison of receptor types.RESULTS: There were no significant differences between the expressions of LPA1 receptors and LPA2 receptors (P ＞ 0.05). Compared with LPA1 receptors and LPA2 receptors (0.79±0.05,0.82±0.06), the LPA3 receptor expression was lower (0.53±0.05, q =23.78,26.53, P＜ 0.01 ).CONCLUSION: There are 3 kinds of LPA receptors in VSMC, and their molecular masses are 600 bp, 463 bp and 899 bp,respectively. There are no differences for the expressions between LPA1 receptors and LPA2 receptors, while the LPA3 receptor expression is less.

] AIM: Lysophosphatidic acid (LPA) is a bioactive phospholipid known to have growth factor-like activity on fibroblasts, and is involved in cardiovascular diseases. Besides direct effects, usually, LPA can work together with other bioactive factors to regulate cardiovascular homeostasis by induction of their expression and production, or increase in their activity. Among variety of bioactive factors, adrenomedullin (ADM) is a multifunctional peptide with an important cytoprotective effect against cardiovascular damage, but the interaction between ADM and LPA on adventitia remains unknown. METHODS: The experiment was performed on the bath of isolated rat aortic adventitia, ADM produced and secreted from adventitia stimulated by LPA was detected by using radioimmunoassay, proliferation in adventitia cells was evaluated by the level of [3H]-thymine incorporation, and prepro ADM gene expression was measured by semi-quantitative reverse transcriptase polymerase chain reaction. RESULTS: It was found that LPA stimulated aortic adventitia to secrete ADM and express its mRNA in a concentration-dependent manner. ADM inhibited LPA-induced proliferation in adventitial cells, and attenuated the activity of mitogen activated protein kinase (MAPK) stimulated by LPA. In contrast, the treatment with specific antagonists of ADM receptor potentiated the LPA-induced proliferation in adventitial cells. CONCLUSION: LPA stimulates adventitia to produce and secrete ADM, and in turn, ADM produced by adventitia regulates the vascular biological effects of LPA. [

Objective To observe the effects of different antithrombotic interventions on the changes of plasma lysophosphatidic acid (LPA) level in patients with nonvalvular atrial fibrillation (NVAF) and to provide the basis for clinical antithrombotic therapy. Methods A total of 235 patients with NVAF who did not receive antithrombotic therapy diagnosed by clinical and auxiliary examinations were randomly allocated to receive aspirin (100 mg/d) plus dipyridamole (100 mg/d) (n =76), aspirin (100 mg/d) plus fixed-dose warfarin (1.25 mg/d) (n =79), and dose-adjusted warfarin (international normalized ratio (INR) range of 1.5 to 2. 1) (n =80). They gore redivided into <60, 60-75, and ≥76 year-old groups according to their age. The plasma LPA levels were measured and compared before treatment and 2 and 6 weeks after treatment. Results 1he plasma LPA levels were decreased more significantly in the aspirin plus fixed-dose group than those in the aspirin plus dipyridamole and dose-adjusted warfarin groups (all P < 0.01). Two and 6 weeks after treatment with aspirin plus dipyridamole in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P<0. 01). Two and6 weeks after treatment with aspirin plus fixed-dose warfarin in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P <0. 01). Two and 6 weeks after treatment with aspirin plus fixed-dose warfarin in the 60-75 year-old group, the plasma LPA levels were significantly lover than those before treatment (all P <0.01). Two and 6 weeks after the treatment with dose-adjusted warfarin (INR 1.5-2. 1) in patients in each age group, the plasma LPA levels were significantly lower than those before treatment. Conclusions 1he different antithromhotic therapeutic modalities have different effects on platelet activation in patients with NVAF in different age groups. The patients in the < 60 year-old group can receive aspirin plus dipyridamole, the patients in the < 75 year-old group can receive aspirin plus fix-dose warfarin, and the patients > 75 year-old, dose-adjusted warfarin (INR 1. 5-2. 1) should he recommend.

Objective: To observe the characteristics of dynamic changes of lysophosphatidic acid (LPA) levels in cerebrospinal fluid (CSF) in patients with subarachnoid hemorrhage (SAH) and its relationship with cerebral vasospasm (CVS) and to explore the pathogenesis of CVS. Methods: Sixty-seven patients with SAH diagnozed by clinical and accessory examinations were selected. The LPA levels in CSF were measured at 24 hours, day 7,14, and 28 respectively after the onset of symptoms,and they were compared with a control group. The correlation between LPA levels and CVS on the time course was also observed at the same time. Results: Of the 67 patients with SAH, a total of 29 patients (43.3%) occurred CVS, the average time of occurrence was 6. 6 days. There was no significant difference between the LPA levels in CSF in patients with SAH and the control group at 24 hours after the onset of symptoms; they were significantly higher than the control group at day 7 (P ＜0. 001); they were significantly higher than the control group at day 14 (P ＜ 0. 001), but they were significantly lower than those at day 7 (P ＜ 0. 01); they decreased to baseline at day 28, and there was significant difference compared with the control group. There was no significant difference between the LPA levels in the CVS group and those in the non-CVS group at 24 hours, they were significantly higher than those in the non-CVS group at day 7 (P ＜0. 001), they were still significantly higher than those in the non-CVS group at day 14 (P ＜0. 01); and there was no significant difference between the 2 groups at day 28. Conclusions: The LPA levels in CSF in patients with SAH increased significantly from day 7 to day 14 after the onset of symptoms, and they had obvious association with CVS on the time course. The detection of the LPA levels in CSF may have important significance in predicting the occurrence of CVS.